During epithelial-mesenchymal interactions in numerous epidermal organ systems, there is an assumed transfer of differentiative signals between tissues. This transfer has been indirectly confirmed by heterotypic cell recombination experiments, transfilter experiments and the diffusion of various isotopic precursors from one tissue to the other in vivo and in vitro. A variety of complex embryonic organs consist of epithelial and mesenchymal components and in general, mesenchymal cells have been found to "direct" the differentiation of epithelial components. Thus, a system has been defined which appears to rely on inductive influences from one cell to another with the concomitant differentiation of the second cell. Several important questions arising from these observations concern the nature, reception and translation of the inducing agent or signal. Recent observations suggest that the mechanisms of induction may be mediated at the plasma membrane; and for this reason, the focus of our proposed research concerns detailed investigations of membrane events. We propose to investigate cell surface events of induction by carrying out tissue recombination and induction experiments using embryonic tooth organs in our newly-developed culture system. Specifically, we will: (1) study the nature of the mesenchymal stimulus which signals epithelial differentiation; (2) investigate the transmission of the signal at the epithelial cell plasma membrane; (3) study the contribution of selective proteolysis to inductional events; (4) study the hormonal regulation of mesenchymal-epithelial interactions; and (5) introduce experiments involving recombination of heterologous tissues derived from normal and mutant mice which show abnormalities in the development of epidermal organs including teeth.